Prognostic Stratification and Subtyping of Glioblastoma Using Transient Receptor Potential Channels.

Background: Transient receptor potential (TRP) channels regulate Ca Methods: We curated a comprehensive compendium of 522 TRP-related genes from MSigDB, KEGG, and GeneCards. Differential expression analysis across clinical variables in The Cancer Genome Atlas Glioblastoma cohort (TCGA-GBM; Results: TRPRS robustly stratified GBM patients into high- and low-risk groups with significantly distinct overall survival across all four datasets (AUC = 0.72-0.81). Genomically, high-TRPRS tumors were enriched for PTEN loss and 9q21.3 amplification, whereas low-TRPRS tumors frequently harbored TP53 mutations and 1q21.3 deletions. High TRPRS was associated with diminished cytotoxic T-cell infiltration and predicted resistance to multiple therapeutics-including cisplatin, carmustine, gefitinib, buparlisib, and afatinib. Notably, TIDE analysis revealed significantly reduced likelihood of response to immune checkpoint blockade in high-TRPRS GBM, a pattern consistently observed in immunotherapy-treated cohorts of melanoma, renal cell carcinoma, and bladder cancer. Functional assays demonstrated that IFNGR2 knockdown suppressed glioma cell proliferation and attenuated NF- Discussion: TRPRS provides a robust, biologically grounded tool for simultaneous prognostication and therapy guidance in GBM, highlighting TRP signaling as a therapeutic vulnerability.